Omics · study · 2026
RNA-Seq analysis of PNA-mediated knockdown of the colibactin regulator ClbR in uropathogenic Escherichia coli CCR20
Listed in NCBI GEO
Antisense oligomers (ASOs) offer a sequence-specific strategy to reprogram bacterial gene expression.
Description
Currently, they have primarily been used as antimicrobials targeting mRNAs of essential genes. By contrast, their potential to selectively suppress harmful genes in members of the microbiota without eliminating these bacteria is underexplored.
Here, we investigated the use of ASOs to repress the biosynthesis of the genotoxin colibactin in Escherichia coli. Colibactin, a secondary metabolite of Enterobacteriaceae harboring the polyketide synthase (pks) island, has been linked to the development of colorectal cancer. We show that peptide nucleic acid (PNA)- based ASOs against different pks island mRNAs (clbA, clbP, clbQ, and clbR) selectively blocked protein synthesis in vitro and in the colorectal cancer isolate E. coli CCR20 pks+ .
Read the rest (1 more)
Moreover, clbR- targeting ASOs effectively reduced colibactin-induced DNA damage in infected HeLa cells, indicating that clbR, which encodes the transcriptional activator of the pks island, is a particularly potent target to disrupt colibactin production. Clinically relevant phosphorodiamidate morpholino (PMO)-based ASOs were equally effective as PNA-based ASOs. Our work introduces ASOs as a viable RNA-based strategy to inhibit secondary metabolite production and pioneers a nongenetic approach to study biosynthetic gene clusters, which are common in nature and often found in genetically intractable microbes.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE345nnn/GSE345846 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE345846 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1522219 ncbi.nlm.nih.gov/bioproject/PRJNA1522219 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75% · RNA sequencing 65%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE345846 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |